Abstract

The brain plays a vital role in maintaining homeostasis and effective interaction with the environment, shaped by genetic and environmental factors throughout neurodevelopment and maturity. While genetic components dictate initial neurodevelopment stages, epigenetics—specifically neuroepigenetics—modulates gene expression in response to environmental influences, allowing for brain adaptability and plasticity. This interplay is particularly evident in neuropathologies like Rett syndrome and CDKL5 deficiency syndrome, where disruptions in neuroepigenetic processes underline significant cognitive and motor impairments. The environmental enrichment paradigm, introduced by Donald Hebb in the late 1940s, demonstrates how enriching stimuli—such as complex sensory, social, and cognitive inputs—affect brain structure and function. Despite methodological variability, evidence reveals that enriched environments catalyze beneficial changes in behavior and neuroanatomy, including increased synaptic plasticity, enhanced motor coordination, and improved cognitive performance in rodent models. Additionally, environmental enrichment induces epigenetic modifications that facilitate these outcomes, highlighting the necessity of understanding the mechanisms driving gene expression changes within the context of enriched experiences. Ultimately, this manifold relationship between environment, neuroepigenetic modulation, and brain function highlights the brain’s capacity for change, reinforcing the importance of considering environmental factors in studies of neurodevelopment and therapy for neurological disorders. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2025.